Erowid References Database
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Leysen JE, Gommeren W.
“Characterization and quantification of serotonin-S2 receptor sites on human blood platelet membranes”.
Archives Internationales de Pharmacodynamie et de Therapie. 1984 November;274(1):172.
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Abstract
The biniding of 3H-lysergic acid diethylamide (3H-LSD, spec. radioactivity 70.3 Ci/mmole) to human blood platelet membranes, obtained from drug-free, healthy volunteers was studied. One ml of platelet membrane preparations in Tris-HCL buffer pH 7.3 (50mM, 120 mM NaCl, 5 mM Kcl, 2 mM MgCl2), corresponding to 5 10 platelets per ml, were incubated with 3H-LSD at 37 degrees C for 240 min. Incubation was stopped and labelled membranes collected by a rapid filtration procedure. Specific binding, defined by inhibition with 1000-fold excess spiperone, represented 500f total membrane labelling measured at 1 nM 3H-LSD. Specific 3H-LSD binding was saturable at nanomolar concentrations and Scatchard plots were rectilinear. Determinations in platelet membranes from 27 volunteers revealed a mean Bmax-value =32 (sigma =7) fmoles/10^9 platelets and a KD=1.0 (sigma = 0.4) nM. For 21 individuals the Bmax value was comprised between 26 and 38 fmoles/10^9 platelets, 4 showed a value between 20 and 26 and 2 showed a value higher than 38 fmoles/10^9 platelets. Specific 3H-LSD binding was inhibited by known serotonin antagonists and agonists. IC50 values (in order of potency) were between 10^-9 and 10^-8 M for LSD and ergotamine; between 10^-8 and 10^-7 M for spiperone, ketanserin, pizotifen ~cyproheptadine, methysergide, pipamperone, serotonin; between 10^-7 and 10^-6 M for cinanserin ~ bufotenine, amitriptyline; and IC50 = 1.6 10^-6 M for tryptamine. The relative binding affinities of antagonists for specific 3H-LSD binding sites on human platelet membranes correlated with thoes for serotonin-S2 sites labelled with 3H-ketanserin in frontal cortex tissue. However, the indole-like serotonin agonists and ergots were relatively more potent in the 3H-LSD binding test using platelets than in the 3H-ketanserin binding model using brain tissue. It is concluded that specific 3H-LSD binding to human blood platelet membranes shows features of serotnonin-S2 receptor sites, but a component of indole-recognition site may be involved. The maximal number of binding sites in platelet membranes of volunteers is fairly constant. 3H-LSD binding to human platelet membranes may represent a useful model for investigating serotonin-S2 receptor alterations in diseases and following chronic drug treatment.
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